Confirmation of linkage to bipolar disorder of markers on chromosome 21q was found in the 22 CNG pedigrees and in the 96 NIMH collaborative pedigree series. A new gene on chromosome 18p, isolated in this laboratory, showed evidence for linkage disequilibrium with bipolar disorder in both the 22 CNG and 96 NIMH collaborative pedigrees, raising the possibility that this, or another nearby gene, is the susceptibility gene. A marker on the proximal portion of 21q appeared to be in linkage disequilibrium with illness, in both the 22 CNG pedigrees and the 96 NIMH pedigrees. cDNA selection using primary cDNA and biotinylated chromosome 18 cosmids yielded 30 unique cDNA sequences, 5 of which were encoded by previously known genes. Further sequencing and similarity search indicated that the remaining 25 cDNAs represented novel genes, and they comprise approximately 25% of known unique expressed sequence tag sites and genes on chromosome 18.1.